Lung cancer is one of the most common causes of cancer death worldwide, and non-small cell lung cancer (NSCLC) accounts for nearly 80% of those cases (Greenlee, R. T., et al., (2001) CA Cancer J Clin, 51: 15-36.). Many genetic alterations associated with the development and progression of lung cancer have been reported, but the precise molecular mechanisms remain unclear (Sozzi, G. Eur J Cancer, (2001)37 Suppl 7: S63-73.). Over the last decade, newly developed cytotoxic agents, including paclitaxel, docetaxel, gemcitabine, and vinorelbine, have emerged to offer multiple therapeutic choices for patients with advanced NSCLC; however, each of the new regimens can provide only modest survival benefits as compared to cisplatin-based therapies (Schiller, J. H. et al. (2002) N Engl J Med, 346: 92-98.; Kelly, K., et al. (2001) J Clin Oncol, 19: 3210-3218.). Hence, the development of new therapeutic strategies, such as molecular-targeted agents and antibodies, and cancer vaccines, are eagerly awaited.
Systematic analysis of expression levels of thousands of genes on cDNA microarrays is an effective approach to identifying unknown molecules involved in pathways of carcinogenesis, and can reveal candidate targets for development of novel therapeutics and diagnostics. The present inventors have been attempting to isolate novel molecular targets for diagnosis, treatment and prevention of NSCLC by analyzing genome-wide expression profiles of NSCLC cells on a cDNA microarray containing 23,040 genes, using pure populations of tumor cells prepared from 37 cancer tissues by laser-capture microdissection (Kikuchi, T. et al., Oncogene, (2003) 22: 2192-2205.; Zembutsu, H. et al. (2003) Int J Oncol, 23: 29-39.; Kakiuchi, S. et al. Mol Cancer Res, (2003) 1: 485-499.; Suzuki, C. et al., (2003) Cancer Res, 63: 7038-7041.). Through this genome wide cDNA microarray analysis, 642 up-regulated genes and 806 down-regulated genes have been identified as diagnostic markers and therapeutic targets for NSCLC (WO 2004/31413).